Biological Evaluation of Newly Synthesized Biaryl Guanidine Derivatives to Arrest β-Secretase Enzymatic Activity Involved in Alzheimer’s Disease

Proteases BACE1 (β-secretases) enzymes have been recognized as a promising target associated with Alzheimer’s disease (AD). This study was carried out on the principles of molecular docking, chemical synthesis, and enzymatic inhibition of BACE1 enzymes via biaryl guanidine-based ligands. Based on virtual screening, thirteen different compounds were synthesized and subsequently evaluated via in vitro and in vivo studies. Among them, 1,3-bis(5,6-difluoropyridin-3-yl)guanidine (compound (9)) was found the most potent (IC50=97±0.91 nM) and active to arrest (99%) β-secretase enzymes (FRET assay). Furthermore, it was found to improve the novel object recognition test and Morris water maze test significantly (p